U.S. patent application number 11/815085 was filed with the patent office on 2008-12-25 for nebulizer formulation.
This patent application is currently assigned to Breath Limited , a corporation. Invention is credited to Ian Gardner Cameron McAffer, Peter Ernest Tasko.
Application Number | 20080319006 11/815085 |
Document ID | / |
Family ID | 34307728 |
Filed Date | 2008-12-25 |
United States Patent
Application |
20080319006 |
Kind Code |
A1 |
McAffer; Ian Gardner Cameron ;
et al. |
December 25, 2008 |
Nebulizer Formulation
Abstract
A nebulizer formulation contains levalbuterol and ipratropium in
about 2 ml or less of saline and is used for treatment of COPD and
asthma and other airways diseases and disorders with increased
patient compliance.
Inventors: |
McAffer; Ian Gardner Cameron;
(Kent, GB) ; Tasko; Peter Ernest; (Kent,
GB) |
Correspondence
Address: |
STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
1100 NEW YORK AVENUE, N.W.
WASHINGTON
DC
20005
US
|
Assignee: |
Breath Limited , a
corporation
|
Family ID: |
34307728 |
Appl. No.: |
11/815085 |
Filed: |
January 30, 2006 |
PCT Filed: |
January 30, 2006 |
PCT NO: |
PCT/GB2006/000309 |
371 Date: |
April 1, 2008 |
Current U.S.
Class: |
514/304 |
Current CPC
Class: |
A61P 11/06 20180101;
A61K 9/0078 20130101; A61P 43/00 20180101; A61K 31/46 20130101;
A61K 31/37 20130101; A61K 31/137 20130101; A61K 31/46 20130101;
A61K 31/37 20130101; A61P 11/00 20180101; A61K 2300/00 20130101;
A61K 31/137 20130101; A61K 2300/00 20130101; A61K 2300/00
20130101 |
Class at
Publication: |
514/304 |
International
Class: |
A61K 31/439 20060101
A61K031/439; A61P 11/00 20060101 A61P011/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 31, 2005 |
GB |
0501956.7 |
Claims
1. Use of a formulation comprising levalbuterol and ipratropium in
a pharmaceutically acceptable carrier in the manufacture of a
medicament for the treatment of COPD wherein the medicament is
suitable for administration via a nebuliser ampoule containing not
more that 2.2 ml of said formulation.
2. The use of claim 1, wherein the ampoule contains not less than
0.5 ml of said formulation.
3. The use of claim 1, wherein the ampoule contains about 1.0 to 2
ml of said formulation.
4. The use of claim 1, wherein the ampoule contains about 1.5 ml to
2 ml of said formulation.
5. Use of a formulation comprising levalbuterol and ipratropium in
a pharmaceutically acceptable carrier in the manufacture of a
medicament for the treatment of COPD or asthma.
6. The use of claim 5, wherein the patient has asthma.
7. The use of claim 5, wherein the patient has COPD.
8. The use of claim 5, wherein the formulation contains about 1.25
milligrams of levalbuterol.
9. The use of claim 5, wherein the formulation contains about 0.5
milligrams of ipratropium.
10. A filled ampoule containing a formulation comprising
levalbuterol and ipratropium, and a pharmaceutically acceptable
carrier.
11. The filled ampoule of claim 10, containing 2.2 ml or less of
said formulation.
12. The filled ampoule of claim 10, containing 2.0 ml or less of
said formulation.
13. The filled ampoule of claim 10, containing about 1.0 to 2 ml of
said formulation.
14. Use of a formulation comprising levalbuterol and an
anticholinergic agent in a pharmaceutically acceptable carrier in
the manufacture of a medicament for increasing patient compliance
in use of a nebuliser formulation wherein the medicament is
suitable for administration via an ampoule containing not more than
2.2 ml and not less than 0.3 ml of said formulation.
15. The use of claim 14, wherein the ampoule contains not more than
2 ml and not less than 0.5 ml of said formulation.
16. The use of claim 14, wherein the formulation contains from 0.75
to 2.0 mg of levalbuterol.
17. The use of claim 14, wherein the formulation contains from 1.0
to 1.5 mg of levalbuterol.
18. The use of claim 14, wherein the formulation contains from 0.25
to 1.0 mg of ipratropium.
19. The use of claim 14, wherein the formulation contains from 0.4
to 0.7 mg of ipratropium.
20. A kit comprising: (1) a container, containing a single unit
dose of 2.2 ml or less in volume of a therapeutically effective
amount of levalbuterol and an anticholinergic agent, and a
pharmaceutically acceptable carrier; and (2) instructions on how
the dose is to be used.
21. The kit of claim 20, wherein and the instructions explain that
the single unit dose can be administered in less time than a
previously known formulation.
22. The kit of claim 20, wherein the instructions explain that the
patient should continue administering the dose until the complete
dose has been administered.
23. The kit of claim 20, wherein the single unit dose is about 2.0
ml in volume.
24. The kit of claim 23, wherein the volume is about 1.5 ml.
25. The kit of claim 20, wherein the anticholinergic agent is
selected from the group consisting of ipratropium, tiaproprium and
cromolyn sodium.
26. The kit of claim 25, wherein the anticholinergic agent is
ipratropium.
27. The kit of claim 20, comprising instructions to deliver the
dose using a high efficiency nebuliser.
28. The kit of claim 27 wherein the nebuliser is a jet
nebuliser.
29. The kit of claim 20, comprising at least 25 of said single unit
doses.
30. The kit of claim 29, comprising at least 120 of said single
unit doses.
Description
BACKGROUND OF THE INVENTION
[0001] The present invention relates to a nebulizer formulation, in
particular a nebulizer formulation and a method of treatment for
diseases such as Chronic Obstructive Pulmonary Disease (COPD) and
asthma using the formulation.
[0002] Nebulizers provide a means of administering drugs to the
airways of a patient whilst the patient breathes at an
approximately normal rate. They are particularly suitable for
patients who are unable, whether due to age or injury or otherwise,
to inhale at the much higher rates required for administration of
drugs via metered dose inhalers or dry powder inhalers and for
patients who cannot for whatever reason coordinate the activation
of the metered dose inhaler with their inhalation of breath. The
nebulizer apparatus creates a vapour containing drug particles and
the patient breathes the vapour via a mouthpiece or mask attached
to the nebulizer. Typically, nebulizers are used to deliver drugs
for the treatment of airways disorders such as asthma and COPD.
[0003] According to the U.S. Centers for Disease Control and
Prevention, COPD is currently the fourth leading cause of death in
the U.S. (behind heart disease, cancer and stroke), claiming the
lives of in excess of 100,000 Americans annually. An estimated 16
million Americans have been diagnosed with some form of COPD, and
as many as 16 million others have the condition but have not yet
been diagnosed. COPD is hence regarded as a major and growing
health care threat in the U.S. and throughout the rest of the
world.
[0004] A known formulation for treatment of COPD comprises
albuterol (also known as salbutamol) and ipratropium in an ampoule
containing 3.0 ml of solution, and is described in WO 03/037159 and
the equivalent U.S. Pat. No. 6,632,842. In use, the contents of the
ampoule are poured into the chamber of the nebulizer and the
patient then breathes the vapour generated until the ampoule
contents are used. Treatment is typically required up to 4 times
per day, at regular intervals.
[0005] Low patient compliance is a known problem with nebulized
drugs generally, as the period of nebulizing required to administer
a dose is long, typically tens of minutes, perhaps half-an-hour for
a typical dose. Children and adults can become bored during this
period. Patients who stop nebulizing prematurely do not receive a
full dose. This can in turn lead to further reduced patient
compliance as the inadequate dose fails to provide adequate
therapy, discouraging further use.
[0006] It is an object of the present invention to provide
formulations and their uses which overcome or at least ameliorate
one or more of the above-identified problems.
SUMMARY OF THE INVENTION
[0007] The present invention provides novel nebulizer formulations,
suitable for treatment of COPD, asthma and other conditions
associated with reversible obstruction of the airways. The
formulations can be utilized in a variety of known nebulizer
apparatus with reduced wastage of ingredients and/or increased
patient compliance.
[0008] The invention provides a method of treatment of COPD, asthma
and other conditions associated with reversible obstruction of the
airways comprising administering, via a nebulizer, a formulation
containing both levalbuterol and an anticholinergic agent in a
pharmaceutically acceptable carrier.
[0009] More specifically, the present invention provides a method
of treatment of COPD, asthma and other conditions associated with
reversible obstruction of the airways, comprising providing a
nebulizer and an ampoule containing not more than 2.2 ml of a
formulation comprising levalbuterol and an anticholinergic agent,
such as ipratropium, in a pharmaceutically acceptable carrier, and
administering the formulation using the nebulizer.
[0010] A filled ampoule of the invention contains a formulation of
levalbuterol and an anticholinergic agent, e.g. ipratropium, and a
more specific ampoule contains a nebulizer formulation, wherein the
formulation contains from 1.0 to 1.5 mg of levalbuterol, and from
0.40 to 0.70 mg of ipratropium, in a total volume of from 0.3 to 5
ml.
[0011] Also provided by the invention is a method of increasing
patient compliance in use of a nebulizer formulation, comprising
providing a nebulizer, and an ampoule containing said formulation,
wherein the formulation comprises levalbuterol and an
anticholinergic agent in a pharmaceutically acceptable carrier and
wherein the ampoule contains not more than 2.2 ml and not less than
0.3 ml of said formulation, and administering the formulation using
the nebulizer.
[0012] A kit of the invention comprises a formulation of the
invention with instructions on how to use it.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0013] The invention enables use of nebulizer formulations without
the lower limit on volume typically associated with the art. The
beta agonist is formulated with and administered with an
anticholinergic agent, suitably selected from ipratropium,
tiaproprium, cromolyn sodium and other anticholinergic agents.
[0014] Reference to these active agents herein is intended to refer
also to pharmaceutically acceptable derivatives thereof, such as
but not limited to salts, esters, enol ethers, enol esters, acids,
bases, solvates, hydrates or prodrugs thereof. Ipratropium is an
anticholinergic agent and has a bronchodilator effect, and can thus
aid delivery of, and act in synergy with the bronchodilator effect
of, levalbuterol. Reference to ipratropium thus includes, but is
not limited to, any form of ipratropium which has an
anticholinergic effect in patients suffering from COPD, including,
but not limited to, all automatic forms, enantiomer forms,
stereoisomer, anhydrides, acid addition salts, base salts,
solvates, analogues and derivatives of ipratropium.
[0015] Several acceptable salts of ipratropium exist and for the
invention these may include, but are not limited to, halide salts
such as bromide, chloride and iodide, described for example in U.S.
Pat. No. 3,505,337, which is incorporated herein by reference.
[0016] A method of treatment of COPD or asthma using the teachings
of the invention comprises administering to a human patient, via a
nebulizer, a formulation containing effective amounts of both
levalbuterol and ipratropium in a pharmaceutically acceptable
carrier, and it is expected, using this ampoule formulation, to
achieve improved acceptance of the medicine and better patient
compliance.
[0017] A further anticipated advantage is that the concentration of
the active ingredients can be increased, with the result that
ampoules of the invention can contain reduced volume whilst
retaining substantially the same unit dosage of drug to be
administered. In one embodiment of the invention overall ampoule
concentration (ie. including active and inactive ingredients) is
substantially the same as in previous formulations but ampoule
volume is approximately half. With reduced volume, there is reduced
nebulizing time. This will further improve patient compliance as
there is less time e.g. for patients to become bored or distracted
whilst using the nebulizer.
[0018] In preferred embodiments of the invention, both ampoule
volume is reduced, enabling reduced nebulising time, and ampoule
concentration is reduced.
[0019] The compositions provided herein are used for treating,
preventing, or ameliorating one or more symptoms of a
bronchoconstrictive disorder or disease in a human subject. In one
embodiment, the method includes nebulizer administration to a
subject of an effective amount of a composition containing
levalbuterol and an anticholinergic, whereby the disease or
disorder is treated or prevented.
[0020] The invention relates in particular to formulations for
treatment of COPD and asthma, including, but not limited to,
chronic bronchitis, emphysema, and associated cor pulmonale (heart
disease secondary to disease of the lungs and respiratory system)
with pulmonary hypertension, right ventricular hypertrophy and
right heart failure, and also bronchial asthma, allergic asthma and
intrinsic asthma, e.g., late asthma and airway
hyper-responsiveness.
[0021] The formulations of the present invention are designed for
administration by nebulizer. A nebulized solution is one dispersed
in air to form an aerosol, and a nebulizer generates very fine
liquid droplets suitable for inhalation into the lung. Nebulizers
typically use compressed air, ultrasonic waves, or a vibrating mesh
to create a mist of the droplets and may also have a baffle to
remove larger droplets from the mist by impaction. A variety of
nebulizers are available for this purpose, such as ultrasonic
nebulizers, jet nebulizers and breath-actuated nebulizers. In use,
mouthpieces or masks are typically attached to a patient to aid
delivery of the nebulized solution.
[0022] In preferred embodiments of the invention, formulations are
for delivery with and patients are treated using a high efficiency
nebulizer, in particular one that can deliver at least 15%,
preferably at least 25%, more preferably at least 35% of the drug
substance to the patient's lungs.
[0023] In specific embodiments of the invention, formulations are
delivered using a high efficiency jet nebulizer, a high efficiency
ultrasonic nebulizer or a high efficiency vibrating mesh nebulizer,
use of these devices enabling and/or enhancing the use of the
reduced volume formulations of the invention. Jet nebulizers are
particularly preferred, and one example is the PARI LC Plus
(registered trade mark, Pari GmbH, Germany) nebulizer.
[0024] The invention is of particular application to COPD.
Specifically, a method of treatment of COPD according to the
present invention hence comprises:
[0025] (1) providing: [0026] a) a nebulizer, and [0027] b) an
ampoule containing not more than 2.2 ml of a formulation comprising
levalbuterol and ipratropium in a pharmaceutically acceptable
carrier, and
[0028] (2) administering the formulation using the nebulizer.
[0029] Preferably, the invention provides and uses ampoules which
contain not less than 0.5 ml of formulation, more preferably about
1.0 to 2 ml of said formulation, and very preferably about 1.5 ml
to 2 ml of said formulation. These reduced volumes can lead to
significant reductions in treatment times, with the expected
advantages explained.
[0030] Formulations and compositions of the invention generally
comprise a pharmaceutically acceptable carrier. The carrier is
preferably a liquid carrier. Further, the carrier preferably
comprises water and may comprise other components.
[0031] A filled ampoule of the invention contains a formulation of
levalbuterol and ipratropium. This is generally in a
pharmaceutically acceptable carrier and buffered for human use to a
pH of about 3.5-5.5. The formulations of the examples are buffered
to about pH 4. The levalbuterol is used in the examples as the HCl
salt, though other salts are suitable, and the ipratropium is
generally used as its HBr salt, though again other salts are
suitable. HCl is conveniently used for pH adjustment. The
formulations are free of preservative, which is an advantage as
some preservatives can be associated with bronchoconstrictor
effects--the opposite effect to that required by the formulation.
Water is used to provide the carrier, and water for injection is
preferred due to its purity.
[0032] One or more tonicity adjusting agents may be added to
provide the desired ionic strength. Tonicity adjusting agents for
use herein include those which display no or only negligible
pharmacological activity after administration. Both inorganic and
organic tonicity adjusting agents may be used. Compositions of the
invention can also include excipients and/or additives. Examples of
these are surfactants, stabilizers, complexing agents,
antioxidants, or preservatives which prolong the duration of use of
the finished pharmaceutical formulation, flavorings, vitamins, or
other additives known in the art. Complexing agents include, but
are not limited to, ethylenediaminetetraacetic acid (EDTA) or a
salt thereof, such as the disodium salt, citric acid,
nitrilotriacetic acid and the salts thereof. In one embodiment, the
complexing agent is EDTA. Preservatives include, but are not
limited to, those that protect the solution from contamination with
pathogenic particles, including benzalkonium chloride or benzoic
acid, or benzoates such as sodium benzoate. Antioxidants include,
but are not limited to, vitamins, provitamins, ascorbic acid,
vitamin E or salts or esters thereof.
[0033] Formulations as described in this invention can be readily
prepared by a person of skill in the art. In one method, a solution
of NaCl is prepared with concentration approximately 9 g/l. To this
are added ipratropium bromide to a concentration as desired, but
typically about 0.25 mg/ml and levalbuterol, again to the
concentration desired but typically about 0.625 mg/ml. HCl is then
added to give a final pH of about 4.0. This formulation can be
filled into ampoules using blow fill seal technology (described in
more detail below) to yield ampoules with the required extractable
volume of formulation.
[0034] Reference to an ampoule with a specified volume and to the
extractable volume of an ampoule refer to the volume of solution
that can be extracted from the ampoule in normal use, e.g. by
breaking it open and pouring out the contents without actively
flushing the ampoule or carrying out scientific extraction methods.
There is in addition some tolerance in the volumes recited, as
filling machines vary in their accuracy. By way of illustration,
"an ampoule containing 3 ml of solution" and a "3 ml ampoule", say,
both refer to an ampoule which contains about 3.1 to about 3.2,
generally about 3.15, ml of solution and which when opened and
poured into the nebulizer results in approximately 3 ml of solution
being transferred into the nebulizer. Hence, the volumes recited
refer to the amount of solution that can be readily extracted from
the ampoule rather than the amount the ampoule is filled with.
[0035] Preferred embodiments of the invention provide methods and
ampoules for adults, for whom a typical dose of levalbuterol is
about 1.25 milligrams. A typical dose of ipratropium is about 0.5
milligrams. Ampoules thus suitably contain such amounts of the
active ingredients in their extractable volume.
[0036] Preferably, ampoules of the invention have reduced volume,
containing 2.2 ml or less of said formulation, preferably 2.0 ml or
less of said formulation or about 1.0 to 2 ml of said formulation.
Specific embodiments of the invention, set out in detail below,
provide ampoules of about 2 ml. Other suitable ampoule volumes are
about 1.5 ml, about 1.0 ml and about 0.5 ml.
[0037] In use of the formulations of the invention, it is possible
to deliver a sufficient dose of ipratropium and levalbuterol in a
shorter period of time than is necessary for known combination
formulations. Hence, the invention provides in another aspect a
method of increasing patient compliance in use of a nebulizer
formulation, comprising
[0038] (1) providing: [0039] a) a nebulizer, and [0040] b) an
ampoule containing said formulation, wherein the formulation
comprises levalbuterol and ipratropium in a pharmaceutically
acceptable carrier and wherein the ampoule contains not more than
2.2 ml and not less than 0.3 ml of said formulation, and
[0041] (2) administering the formulation using the nebulizer.
[0042] The volume of the ampoule can be reduced following the
teachings of the invention. However, there is a practical limit to
the concentration of the contents of ampoules of the invention in
as much as very small amounts of highly concentrated liquids are
easily spilled and are not so easy to dispense accurately. In
preferred methods and formulations, the ampoules contain not more
than 2 ml and not less than 0.5 ml of said formulation.
[0043] The formulation used in the method typically contains from
0.75 to 2.0 mg of levalbuterol, preferably from 1.0 to 1.5 mg of
levalbuterol. The formulation also typically contains from 0.25 to
1.0 mg of ipratropium, preferably from 0.40 to 0.70 mg of
ipratropium. These formulations preferably have volumes of about
2.0 ml, about 1.5 ml, about 1.0 ml or about 0.5 ml.
[0044] A specific ampoule contains a nebulizer formulation of:
[0045] a) from 1.0 to 1.5 mg of levalbuterol, and [0046] b) from
0.40 to 0.70 mg of ipratropium, in a volume of from 0.3 to 2.2
ml.
[0047] The total volume is preferably from 0.5 ml to 2 ml, and more
preferably has a total volume of about 2 ml or about 1.5 ml.
[0048] In use of the invention, increased concentration of the
active ingredients, ipratropium and levalbuterol, enables smaller
volumes of the formulation to be used. Generally, the levalbuterol
is present at about 0.57 mg/ml or higher, about 0.63 mg/ml or
higher or about 0.83 mg/ml or higher. An ampoule with an
extractable volume of 0.5 ml can contain levalbuterol at about 2.5
mg/ml. The ipratropium is generally present at a concentration of
about 0.23 mg/ml or higher, about 0.25 mg/ml or higher or about
0.33 mg/ml or higher. An ampoule with an extractable volume of 0.5
ml can contain ipratropium at about 1 mg/ml.
[0049] Pharmaceutical compositions containing levalbuterol and an
anticholinergic agent for administration via nebulization are hence
provided. The compositions are preferably sterile filtered and
filled in ampoules or vials, including unit dose vials, providing
sterile unit dose formulations for use in a nebulizer.
[0050] In a further embodiment, the present invention provides a
container containing a vial, comprising a single unit dose of a
therapeutically effective amount of levalbuterol and ipratropium in
a sterile solution, or a plurality of such vials. The extractable
volume of each unit dose of a specific embodiment of the invention
comprises about 1.25 mg of levalbuterol (or equivalent amount of a
derivative thereof) and about 0.5 mg ipratropium bromide (or
equivalent amount of a derivative thereof) in a sterile, aqueous
solution. The solution contains sodium chloride at about 9 mg/ml to
make the solution isotonic and hydrochloric acid to adjust pH of
the solution to about 4.0. It is optional to include a chelating
agent, such as EDTA. The volume is preferably about 2.0 ml or about
1.5 ml.
[0051] The invention additionally provides kits for use in
treatment of the diseases described herein. The kits comprise:
[0052] (1) a container, containing a single unit dose of a
therapeutically effective amount of levalbuterol plus an
anticholinergic agent; and [0053] (2) instructions on how the dose
is to be used.
[0054] The single unit dose is suitably as described elsewhere
herein in relation to formulations of the invention. The
instructions instruct the patient as to how the dose should be used
in conjunction with a nebulizer, such as how to open it and
transfer its contents into the nebulizer, how to operate the
nebulizer and for how long nebulizing should be continued to
complete administration of the dose.
[0055] Kits of the invention can contain a plurality of single unit
doses. One kit comprises at least 120 or at least 125 single unit
doses, being designed to provide one month's worth of doses to be
taken 4 times per day. Another kit comprises at least 25 or at
least 28 single unit doses, designed for a week's supply at 4 per
day. Other kits may usefully contain 30 or 60 single unit
doses.
[0056] For embodiments of the invention in which the extractable
volume is 2.2 ml or less, especially where the volume is 2.0 ml or
1.5 ml or lower, the instructions may explain that the present
formulation can be administered in less time than a previously
known formulation, such as a known 3 ml formulation, hence
reinforcing this advantage of the invention and improving the
prospects for increased patient compliance. Preferably, the
instructions explain that the patient should continue administering
the dose until the complete dose has been administered.
[0057] Formulations of the invention are suitable for filing into
ampoules using "blow fill seal" (BFS) methods. The principle is
that a plastic parison is extruded from polymer, formed into a
container, filled and sealed in a single aseptic operation. BFS is
now the preferred method for aseptic manufacture of ampoules due to
the flexibility in container design, overall product quality,
product output and low operational costs. Fill accuracies of better
than .+-.5% have been demonstrated for container volumes as small
as 0.5 ml and hence BFS is suitable for manufacture of ampoules
according to the invention.
[0058] One BFS operation includes the multi-step process of blow
moulding, aseptic filling and hermetic sealing of liquid products
with fill volumes ranging from 0.1 ml to 1,000 ml, though for
ampoules volumes in the range 0.5 ml to 5 ml are more common. A
variety of polymers may be used in the process; low and
high-density polyethylene and polypropylene are the most
popular.
[0059] Furthermore, the BFS process flow is normally impacted by
only two raw materials--product and polymer--that are each
processed inline, thereby making the process amenable to large
uninterrupted batch sizes, some in excess of 500,000 or 1,000,000
units, and fill durations of up to 120 hours.
[0060] In a typical operation, to form the container, thermoplastic
is continuously extruded in a tubular shape. When the tube reaches
the proper length, the mould closes and the parison is cut. The
bottom of the parison is pinched, closed and the top is held in
place with a set of holding jaws. The mould is then transferred to
a position under the filling station. To fill the container, the
nozzle assembly lowers into the parison until the nozzles form a
seal with the neck of the mould. Container formation is completed
by applying vacuum on the mould side of the container and by
blowing sterile filtered air into the interior of the container.
The fill system delivers a precise dosage of product into the
container. The nozzles retract into their original position.
Lastly, to seal the container, following completion of the filling
process, the top of the container remains semi-molten. Separate
seal moulds close to form the top and hermetically seal the
container. The moulds open and the container is then conveyed out
of the machine. The whole of the above process is operated in
pharmaceutical aseptic processing conditions.
[0061] BFS machines are commercially available from a number of
suppliers, including Weiler Engineering, Inc (US) and rommelag USA
Inc (US).
[0062] The invention is now illustrated in the following
non-limiting examples.
EXAMPLES
Example 1
[0063] A bulk nebulizer formulation was prepared having the
following composition:
TABLE-US-00001 Component Amount/Concentration Levalbuterol 0.625
mg/ml Ipratropium 0.25 mg/ml NaCl solution (for injection) 9 mg/ml
HCl To adjust pH to 4.0
[0064] The formulation was loaded into 2 ml (extractable volume),
twist-top plastic ampoules.
Example 2
[0065] A bulk nebulizer formulation was prepared having the
following composition:
TABLE-US-00002 Component Amount/Concentration Levalbuterol 0.83
mg/ml Ipratropium 0.33 mg/ml NaCl solution (for injection) 9 mg/ml
HCl To adjust pH to 4.0
[0066] The formulation was loaded into 1.5 ml (extractable volume),
twist-top plastic ampoules.
[0067] The invention hence provides nebulizer formulations and uses
thereof.
* * * * *